Insights Into the Pathogenesis of Bullous Pemphigoid: The Role of Complement-Independent Mechanisms

Abstract

Bullous pemphigoid is an autoimmune blistering disease caused by autoantibodies targeting BP180 and BP230. While deposits of IgG and/or complement along the epidermal basement membrane are typically seen suggesting complement -mediated pathogenesis, several recent lines of evidence point towards complement-independent pathways contributing to tissue damage and subepidermal blister formation. Notable pathways include macropinocytosis of IgG-BP180 complexes resulting in depletion of cellular BP180, direct induction of pro-inflammatory cytokines from keratinocytes, as well as IgE autoantibody- and eosinophil-mediated effects. We review these mechanisms which open new perspectives on novel targeted treatment modalities.

Adaptive and innate immune pathogenesis of bullous pemphigoid: A review

“…Autoantibody binding to pathogenic antigen cause the separation of the BMZ in a complement-dependent or -independent manner ( 5 , 21 , 85 , 118 ) ( Figure 1 ). Antigen–IgG1 binding to the BMZ triggers complement activation.…”

“…The pathogenesis of pemphigoid is unclear, but autoantibodies to the hemidesmosome are implicated. Subepidermal blister formation with obvious inflammatory-cell infiltration is a hallmark of BP but not pemphigus disease ( 5 ). The pathogenesis of BP involves various immune cells and factors, including B cells ( 6 ), T cells ( 7 ), complement cells ( 5 ), mast cells ( 8 ), neutrophils ( 9 ), and eosinophils ( 10 ).…”

“…Subepidermal blister formation with obvious inflammatory-cell infiltration is a hallmark of BP but not pemphigus disease ( 5 ). The pathogenesis of BP involves various immune cells and factors, including B cells ( 6 ), T cells ( 7 ), complement cells ( 5 ), mast cells ( 8 ), neutrophils ( 9 ), and eosinophils ( 10 ). The pathogenetic role of interactions among the aforementioned types of inflammatory cells is unclear.…”

Recurrent bullous pemphigoid: A case report and literature review

“…The majority of patients with BP develop, apart from IgG, IgA and IgE anti-BP180 reactivity. IgE anti-BP180 NC16A antibodies are associated with a severe form of BP, a longer duration for remission, and the requirement for more intensive therapies (4). BP230 (also known as BPAG1-e and BPAG1) is recognized by 50-70% of BP sera.…”

“…The expression of ICAM-1 on keratinocytes is induced in basal and lower suprabasal layers by IFN-γ and TNF-α, which are products released by lymphocytes infiltrating inflamed skin. Activated lymphocyte IFN-γ induces the keratinocyte expression of ICAM-1 and HLA-DR, promoting inflammatory and allergic epidermal responses (4,16).…”